Shakya Akhilesh Kumar, Nandakumar Kutty Selva
Department of Chemical Engineering, Texas Tech University, Lubbock, Texas.
Curr Protoc Mouse Biol. 2014 Mar 21;4(1):11-24. doi: 10.1002/9780470942390.mo130226.
Collagen-induced arthritis (CIA), the classical animal model for experimental arthritis, resembles human rheumatoid arthritis in several aspects. However, the most widely used method of inducing CIA utilizes Freund's adjuvants, which can skew the elicited immune responses and also pose toxicity problems. This unit describes a new method of inducing CIA using a well defined stimuli-responsive synthetic polymer, poly-N-isopropylacrylamide-based adjuvant, mixed with the joint cartilage protein collagen type II (CII). PNiPAAm as an adjuvant is biodegradable and biocompatible, and does not skew immune responses. Thus, it is helpful in the development of arthritis models for studying antigen and tissue -specific autoimmune responses in an unbiased manner. This model is valuable for analyzing disease pathways, positional identification of genes regulating arthritis, validation of existing therapies, and exploring new therapeutic targets. Furthermore, this newly developed PNiPAAm adjuvant allows investigation of disease induction using specific autoantigens in several autoimmune diseases independently of toll-like receptors, as well as optimization of vaccine delivery systems for infectious diseases.
胶原诱导性关节炎（CIA）是实验性关节炎的经典动物模型，在多个方面与人类类风湿性关节炎相似。然而，诱导CIA最常用的方法是使用弗氏佐剂，这种佐剂会使引发的免疫反应产生偏差，还会带来毒性问题。本单元介绍了一种诱导CIA的新方法，即使用一种定义明确的刺激响应性合成聚合物——基于聚N-异丙基丙烯酰胺的佐剂，与关节软骨蛋白II型胶原（CII）混合使用。作为佐剂的聚N-异丙基丙烯酰胺是可生物降解且生物相容的，不会使免疫反应产生偏差。因此，它有助于开发关节炎模型，以无偏差的方式研究抗原和组织特异性自身免疫反应。该模型对于分析疾病途径、确定调节关节炎的基因位置、验证现有疗法以及探索新的治疗靶点具有重要价值。此外，这种新开发的聚N-异丙基丙烯酰胺佐剂能够独立于Toll样受体，利用几种自身免疫疾病中的特定自身抗原研究疾病诱导过程，还能优化传染病疫苗递送系统。
